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Phosphodiesterase Type 4 Inhibitor Rolipram Improves Survival of Spiral Ganglion Neurons In Vitro

Sensorineural deafness is caused by damage of hair cells followed by degeneration of the spiral ganglion neurons and can be moderated by cochlear implants. However, the benefit of the cochlear implant depends on the excitability of the spiral ganglion neurons. Therefore, current research focuses on...

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Autores principales: Kranz, Katharina, Warnecke, Athanasia, Lenarz, Thomas, Durisin, Martin, Scheper, Verena
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2014
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3958480/
https://www.ncbi.nlm.nih.gov/pubmed/24642701
http://dx.doi.org/10.1371/journal.pone.0092157
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author Kranz, Katharina
Warnecke, Athanasia
Lenarz, Thomas
Durisin, Martin
Scheper, Verena
author_facet Kranz, Katharina
Warnecke, Athanasia
Lenarz, Thomas
Durisin, Martin
Scheper, Verena
author_sort Kranz, Katharina
collection PubMed
description Sensorineural deafness is caused by damage of hair cells followed by degeneration of the spiral ganglion neurons and can be moderated by cochlear implants. However, the benefit of the cochlear implant depends on the excitability of the spiral ganglion neurons. Therefore, current research focuses on the identification of agents that will preserve their degeneration. In this project we investigated the neuroprotective effect of Rolipram as a promising agent to improve the viability of the auditory neurons. It is a pharmaceutical agent that acts by selective inhibition of the phosphodiesterase 4 leading to an increase in cyclic AMP. Different studies reported a neuroprotective effect of Rolipram. However, its significance for the survival of SGN has not been reported so far. Thus, we isolated spiral ganglion cells of neonatal rats for cultivation with different Rolipram concentrations and determined the neuronal survival rate. Furthermore, we examined immunocytologically distinct proteins that might be involved in the neuroprotective signalling pathway of Rolipram and determined endogenous BDNF by ELISA. When applied at a concentration of 0.1 nM, Rolipram improved the survival of SGN in vitro. According to previous studies, our immunocytological data showed that Rolipram application induces the phosphorylation and thereby activation of the transcription factor CREB. This activation can be mediated by the cAMP-PKA-signalling pathway as well as via ERK as a part of the MAP-kinase pathway. However, only in cultures pre-treated with BDNF, an endogenous increase of BDNF was detected. We conclude that Rolipram has the potential to improve the vitality of neonatal auditory nerve cells in vitro. Further investigations are necessary to prove the effect of Rolipram in vivo in the adult organism after lesion of the hair cells and insertion of cochlear implants.
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spelling pubmed-39584802014-03-24 Phosphodiesterase Type 4 Inhibitor Rolipram Improves Survival of Spiral Ganglion Neurons In Vitro Kranz, Katharina Warnecke, Athanasia Lenarz, Thomas Durisin, Martin Scheper, Verena PLoS One Research Article Sensorineural deafness is caused by damage of hair cells followed by degeneration of the spiral ganglion neurons and can be moderated by cochlear implants. However, the benefit of the cochlear implant depends on the excitability of the spiral ganglion neurons. Therefore, current research focuses on the identification of agents that will preserve their degeneration. In this project we investigated the neuroprotective effect of Rolipram as a promising agent to improve the viability of the auditory neurons. It is a pharmaceutical agent that acts by selective inhibition of the phosphodiesterase 4 leading to an increase in cyclic AMP. Different studies reported a neuroprotective effect of Rolipram. However, its significance for the survival of SGN has not been reported so far. Thus, we isolated spiral ganglion cells of neonatal rats for cultivation with different Rolipram concentrations and determined the neuronal survival rate. Furthermore, we examined immunocytologically distinct proteins that might be involved in the neuroprotective signalling pathway of Rolipram and determined endogenous BDNF by ELISA. When applied at a concentration of 0.1 nM, Rolipram improved the survival of SGN in vitro. According to previous studies, our immunocytological data showed that Rolipram application induces the phosphorylation and thereby activation of the transcription factor CREB. This activation can be mediated by the cAMP-PKA-signalling pathway as well as via ERK as a part of the MAP-kinase pathway. However, only in cultures pre-treated with BDNF, an endogenous increase of BDNF was detected. We conclude that Rolipram has the potential to improve the vitality of neonatal auditory nerve cells in vitro. Further investigations are necessary to prove the effect of Rolipram in vivo in the adult organism after lesion of the hair cells and insertion of cochlear implants. Public Library of Science 2014-03-18 /pmc/articles/PMC3958480/ /pubmed/24642701 http://dx.doi.org/10.1371/journal.pone.0092157 Text en © 2014 Kranz et al http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.
spellingShingle Research Article
Kranz, Katharina
Warnecke, Athanasia
Lenarz, Thomas
Durisin, Martin
Scheper, Verena
Phosphodiesterase Type 4 Inhibitor Rolipram Improves Survival of Spiral Ganglion Neurons In Vitro
title Phosphodiesterase Type 4 Inhibitor Rolipram Improves Survival of Spiral Ganglion Neurons In Vitro
title_full Phosphodiesterase Type 4 Inhibitor Rolipram Improves Survival of Spiral Ganglion Neurons In Vitro
title_fullStr Phosphodiesterase Type 4 Inhibitor Rolipram Improves Survival of Spiral Ganglion Neurons In Vitro
title_full_unstemmed Phosphodiesterase Type 4 Inhibitor Rolipram Improves Survival of Spiral Ganglion Neurons In Vitro
title_short Phosphodiesterase Type 4 Inhibitor Rolipram Improves Survival of Spiral Ganglion Neurons In Vitro
title_sort phosphodiesterase type 4 inhibitor rolipram improves survival of spiral ganglion neurons in vitro
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3958480/
https://www.ncbi.nlm.nih.gov/pubmed/24642701
http://dx.doi.org/10.1371/journal.pone.0092157
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